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Vitamin D supplementation appeared to have a modest protective effect against acute respiratory tract infections, especially among people who were very deficient.

Note that the meta-analysis findings may support the introduction of public health measures to improve vitamin D status, although authors of an editorial viewed the results with skepticism.

Vitamin D supplementation appeared to have a modest protective effect against acute respiratory tract infections, especially among people who were very deficient, according to a meta-analysis.

After adjusting for potential confounders such as age, sex, and study duration, vitamin D supplementation was associated with a 12% reduction in the proportion of participants experiencing at least one acute respiratory tract infection, reported Adrian Martineau, PhD, of Queen Mary University of London, and colleagues.

Among participants with baseline vitamin D deficiency (less than 25 nmol/L) a strong protective effect was seen (adjusted odds ratio 0.58, 95% CI 0.40-0.82, number needed to treat =8) in 538 participants in 14 studies (P=0.002), they wrote in BMJ.

The researchers concluded that the meta-analysis findings,"support the introduction of public health measures to improve vitamin D status, particularly in settings where profound vitamin D deficiency is common."

But in an accompanying editorial, Mark Bolland, PhD, of the University of Auckland in New Zealand, and Alison Avenell, MD, of the University of Aberdeen in Scotland, wrote that there are several reasons for viewing the adjusted 12% odds reduction reported by the researchers with skepticism.

"In absolute terms, the primary result is a reduction from 42% to 40% in the proportion of participants experiencing at least one acute respiratory tract infection," they wrote. "It seems unlikely that the general population would consider a 2% absolute risk reduction sufficient justification to take supplements."

Martineau's group searched various databases for randomized, double-blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 which included prospectively collected data on incidence of acute respiratory tract infection. Twenty-five eligible studies, totalling 11,321 participants, were included in the analysis, and individual participant data were available for 10,933 participants (96.6%).

They reported that vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted OR 0.88, 95% CI 0.81-0.96, P<0.001 for heterogeneity).

In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted OR 0.81, 95% CI 0.72-0.91) but not in those receiving one or more bolus doses (adjusted OR 0.97, 95% CI 0.86-1.10; P=0.05 for interaction).

Also, among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L.

Finally, vitamin D did not influence the proportion of participants who experienced at least one serious adverse event (adjusted OR 0.98, 9% CI 0.80-1.20, P=0.83).

The authors noted that patients who did not receive bolus doses experienced the most benefit. "Why might use of bolus dose vitamin D be ineffective for prevention of acute respiratory tract infection?," they wrote. "One explanation relates to the potentially adverse effects of wide fluctuations in circulating 25-hydroxyvitamin D concentrations, which are seen after use of bolus doses but not with daily or weekly supplementation."

Overall, the body of evidence contributing to the analysis was assessed to be of high quality.

Study limitations were limited power to detect effects of vitamin D supplementation for certain subgroups, including those with very low 25-hydroxyvitamin D serum levels receiving bolus dosing regimens, and inadequate data on adherence to study drugs.

Nonetheless, the researchers concluded that their analysis suggests "a major new indication for vitamin D supplementation: the prevention of acute respiratory tract infection."

But Bolland and Avenell stated that the findings "probably not change clinical practice. The results are heterogeneous and not sufficiently applicable to the general population. We think that they should be viewed as hypothesis generating only, requiring confirmation in well-designed, adequately powered controlled trials."

They noted that several such trials are currently underway, and results from these trials are expected within the next few years.

"We consider that current evidence does not support the use of vitamin D supplementation to prevent disease, except for those at high risk of osteomalacia, currently defined as 25-hydroxyvitamin D levels less than 25 nmol/L," they wrote.

This study was funded by the National Health Service's National Institute for Health Research.

Martineau and co-authors disclosed no relevant relationships with industry.

Bolland and Avenell disclosed support from the Health Research Council of New Zealand.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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